Release of Soluble CD30 After Allogeneic Stimulation Is Mediated by Memory T Cells and Regulated by IFN-γ and IL-2

Velásquez, Sonia Y.; García, Luis F.; Opelz, Gerhard; Álvarez, Cristiam M.; Süsal, Caner

doi:10.1097/tp.0b013e318296fd69

Cited by 28 publications

(23 citation statements)

References 45 publications

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“…Significant correlation of maximum sCD30 level or maximum IFN-γ level with CD30 expression on T cells was observed at day 4, but no at day 7 when most surface CD30 had been cleaved and released as soluble CD30. This observation, consistent with previous studies [35], implied that surface CD30 was transiently expressed by activated T cells, but sCD30 could exist for a relatively longer period, and was easily quantified to reflect the maximum cell surface CD30 expression. It is intriguing to speculate that potent proliferating of CD30 + T cells caused by autoantigens exist abundantly in the early phase of SAA, when the disease still hardly been aware because of lacking obvious clinical symptoms.…”

Section: Discussionsupporting

confidence: 92%

Increased Bone Marrow (BM) Plasma Level of Soluble CD30 and Correlations with BM Plasma Level of Interferon (IFN)-γ, CD4/CD8 T-Cell Ratio and Disease Severity in Aplastic Anemia

Zhang

Shi

et al. 2014

PLoS ONE

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Idiopathic aplastic anemia (AA) is an immune-mediated bone marrow failure syndrome. Immune abnormalities such as decreased lymphocyte counts, inverted CD4/CD8 T-cell ratio and increased IFN-γ-producing T cells have been found in AA. CD30, a surface protein belonging to the tumor necrosis factor receptor family and releasing from cell surface as a soluble form (sCD30) after activation, marks a subset of activated T cells secreting IFN-γ when exposed to allogeneic antigens. Our study found elevated BM plasma levels of sCD30 in patients with SAA, which were closely correlated with disease severity, including absolute lymphocyte count (ALC) and absolute netrophil count (ANC). We also noted that sCD30 levels were positively correlated with plasma IFN-γ levels and CD4/CD8 T-cell ratio in patients with SAA. In order to explain these phenomena, we stimulated T cells with alloantigen in vitro and found that CD30+ T cells were the major source of IFN-γ, and induced CD30+ T cells from patients with SAA produced significantly more IFN-γ than that from healthy individuals. In addition, increased proportion of CD8+ T cells in AA showed enhanced allogeneic response by the fact that they expressed more CD30 during allogeneic stimulation. sCD30 levels decreased in patients responded to immunosuppressive therapy. In conclusion, elevated BM plasma levels of sCD30 reflected the enhanced CD30+ T cell-mediated immune response in SAA. CD30 as a molecular marker that transiently expresses on IFN-γ-producing T cells, may participate in mediating bone marrow failure in AA, which also can facilitate our understanding of AA pathogenesis to identify new therapeutic targets.

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Section: Discussionsupporting

confidence: 92%

Increased Bone Marrow (BM) Plasma Level of Soluble CD30 and Correlations with BM Plasma Level of Interferon (IFN)-γ, CD4/CD8 T-Cell Ratio and Disease Severity in Aplastic Anemia

Zhang

Shi

et al. 2014

PLoS ONE

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“…In FADD-deficient mice, studies suggested that FADD is required for the apoptosis mediated by TNFRSF10A and TNFRSF10B [45]. TNFRSF8 interacts with TRAF2 and TRAF5 to mediate the activation of NF- κ B. TNFRSF8 has been reported to limit the proliferative potential of autoreactive CD8 effector T cells and against autoimmunity and positively regulate apoptosis [46]. High-risk FLT3-ITD mutation of acute myeloid leukemia was associated with high TNFRSF8 expression on myeloblasts [47].…”

Section: Discussionmentioning

confidence: 99%

Gene Expression Profiling of Biological Pathway Alterations by Radiation Exposure

Lee

Weng

Hsu

et al. 2014

BioMed Research International

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Though damage caused by radiation has been the focus of rigorous research, the mechanisms through which radiation exerts harmful effects on cells are complex and not well-understood. In particular, the influence of low dose radiation exposure on the regulation of genes and pathways remains unclear. In an attempt to investigate the molecular alterations induced by varying doses of radiation, a genome-wide expression analysis was conducted. Peripheral blood mononuclear cells were collected from five participants and each sample was subjected to 0.5 Gy, 1 Gy, 2.5 Gy, and 5 Gy of cobalt 60 radiation, followed by array-based expression profiling. Gene set enrichment analysis indicated that the immune system and cancer development pathways appeared to be the major affected targets by radiation exposure. Therefore, 1 Gy radioactive exposure seemed to be a critical threshold dosage. In fact, after 1 Gy radiation exposure, expression levels of several genes including FADD, TNFRSF10B, TNFRSF8, TNFRSF10A, TNFSF10, TNFSF8, CASP1, and CASP4 that are associated with carcinogenesis and metabolic disorders showed significant alterations. Our results suggest that exposure to low-dose radiation may elicit changes in metabolic and immune pathways, potentially increasing the risk of immune dysfunctions and metabolic disorders.

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“…In the meantime, there is also a Luminex method with beads that carry antibodies against CD30 [43] . The source of sCD30 seems to be particularly memory T-cells [44] . In recent years, a number of studies have been carried out on the benefit of this biomarker in transplantation medicine [45 -58] .…”

Section: Soluble Cd30 In Serum (Scd30)mentioning

confidence: 99%

Biomarkers in blood for individualization of the pharmacotherapy with immunosuppressive drugs after transplantation of solid organs

Wieland

Shipkova

2015

LaboratoriumsMedizin

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Abstract:The success of transplantation medicine is closely associated with the introduction of potent immunosuppressive drugs. Therapy guidance of the calcineurin inhibitors cyclosporine and tacrolimus as well as the mammalian target of rapamycin (mTOR) inhibitors sirolimus and everolimus is achieved by therapeutic drug monitoring (TDM). For other immunosuppressive drugs such as mycophenolic acid, TDM is not established. It has been suggested that a better individualization of pharmacotherapy could be helpful in avoiding over-and underimmunosuppression, which have been associated with poor long-term outcome of grafts and patients. Therefore, a search for biomarkers that could complement TDM, thereby allowing a better individualization of therapy, is ongoing worldwide. Pharmacodynamic biomarkers in transplantation medicine can be either non-drug-specific, aiming at assessing the global effect on the immune system, or drug-specific, aiming at recording the pharmacologic effect on a drug target. Non-specific pharmacodynamic biomarkers can reflect the degree of immune activation by measuring T-or B-cell activation, the development of operational tolerance by monitoring, e.g., regulatory T-cells, or the graft damage by measuring cell-free DNA released by the graft in response to injury. Drug-specific pharmacodynamic biomarkers have been published for mycophenolic acid, calcineurin, and mTOR inhibitors. The field of biomarker research to complement TDM for a better individualization of immunosuppression is still in its infancy, and controlled prospective clinical trials are needed to unravel or dismiss the potential of particular biomarkers or biomarker combinations in various patient cohorts with different grafts.

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Release of Soluble CD30 After Allogeneic Stimulation Is Mediated by Memory T Cells and Regulated by IFN-γ and IL-2

Cited by 28 publications

References 45 publications

Increased Bone Marrow (BM) Plasma Level of Soluble CD30 and Correlations with BM Plasma Level of Interferon (IFN)-γ, CD4/CD8 T-Cell Ratio and Disease Severity in Aplastic Anemia

Increased Bone Marrow (BM) Plasma Level of Soluble CD30 and Correlations with BM Plasma Level of Interferon (IFN)-γ, CD4/CD8 T-Cell Ratio and Disease Severity in Aplastic Anemia

Gene Expression Profiling of Biological Pathway Alterations by Radiation Exposure

Biomarkers in blood for individualization of the pharmacotherapy with immunosuppressive drugs after transplantation of solid organs

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